Ovarian tumors its staging and management

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Ovarian tumorsSTAGING & MANAGEMENT


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TREATMENT OF OVARIAN CYSTS ANDBENIGN TUMORS

Ovarian cysts < 6 cms usually regress by absorption or spontaneousrupture and the patient may be managed conservatively over 2menstrual cycles with monthly rectovaginal examination.

If regression fails to occur, assessment is indicated

Diagnostic tests include laboratory blood studies and pelvicexamination. Usually, ultrasound studies with and without bloodflow measurements to the involved ovary are used for diagnosis andto help determine the best therapy.

Some tumors require surgery to diagnose accurately, ruling outmalignancy, or to treat. If one ovary must be removed, normalconception and childbirth is possible as long as a normal ovaryremains on the other side.


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Medication

Female hormones or clomiphene may be prescribed.These help shrink or destroy some tumors. Oralcontraceptives are often used as the first step intreatment.


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LAPAROSCOPY

Ovarian cyst and benign tumors can also be resected bythis technique


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Staging The Federation Internationalede Gynecologie et d'Obstetrique

(FIGO) and the American JointCommittee on Cancer (AJCC) have

designated staging.


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Stage I ovarian cancer

limited to the ovaries. Stage IA: tumour limited to 1 ovary, the

capsule is intact, no tumour on ovarian surface

and no malignant cells in ascites or peritonealwashings.

Stage IB: tumour limited to both ovaries,capsules intact, no tumour on ovarian surfaceand no malignant cells in ascites or peritoneal

washings. Stage IC: tumour is limited to 1 or both ovaries

with any of the following: capsule ruptured,tumour on ovarian surface, malignant cells in

ascites or peritoneal washings.


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Stage II ovarian cancer

tumors involving 1 or both ovaries with pelvicextension and/or implants.

Stage IIA: extension and/or implants on the

uterus and/or fallopian tubes. No malignantcells in ascites or peritoneal washings.

Stage IIB: extension to and/or implants onother pelvic tissues. No malignant cells inascites or peritoneal washings.

Stage IIC: Pelvic extension and/or implants(stage IIA or stage IIB) with malignant cells inascites or peritoneal washings.


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Stage III ovarian cancer

tumours involving 1 or both ovaries with microscopicallyconfirmed peritoneal implants outside the pelvis. Superficialliver metastasis equals stage III.

Stage IIIA: microscopic peritoneal metastasis beyond

pelvis (no macroscopic tumour).

Stage IIIB: macroscopic peritoneal metastasis beyondpelvis less than 2 cm in greatest dimension.

Stage IIIC: peritoneal metastasis beyond pelvis greater

than 2 cm in greatest dimension and/or regional lymphnode metastasis.


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Stage IV ovarian cancer

tumours involving 1 or both ovaries with distantmetastasis. Parenchymal liver metastasis equals

stage IV.


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Management


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Treatment Options

The treatment of ovarian cancers based on thestage of the disease which is a reflection of theextent or spread of the cancer to other parts of

the body. It also depends on histologic cell type,and the patient's age and overallcondition.

There are basically three forms of treatment ofovarian cancer: surgery Chemotherapy radiation treatment,


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GENERAL GUIDELINES:

Standard treatment is surgery (staging and optimaldebulking) followed by adjuvant chemotherapy in most

cases. Even if optimal surgery is not possible, removingas much tumor as possible will provide significantpalliation of symptoms.

Borderline lesions may be treated with conservativesurgery


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GENERAL GUIDELINES:

Germ cell tumors are treated with surgery and multi-agent chemotherapy in most cases

Advanced epithelial ovarian cancer is very sensitive tochemotherapy with responses in the range of 70-80% tofirst-line chemotherapy. The majority, however, relapseand ultimately die of chemotherapy-resistant disease.Second-line chemotherapy to date is disappointing in allforms of epithelial ovarian cancer with virtually nochance of successful second-line treatment followingfailure of initial regime.


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SURGERY


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Treatment of OvarianEpithelial Cancer


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Stage I

Generally a total abdominal hysterectomy, removal ofboth ovaries and fallopian tubes, omentectomy, biopsy

of lymph nodes and other tissues in the pelvis andabdomen,is done. Young women whose disease isconfined to one ovary are often treated by a unilateralsalpingo-oophorectomy without a hysterectomy andremoval of the opposite ovary being performed

Depending on the pathologist's interpretation of thetissue removed, there may be no further treatment if thecancer is low grade, or if the tumor is high grade thepatient may receive combination chemotherapy.


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Stage II

Treatment is almost always hysterectomy and bilateral

salpingo-oophorectomy as well as debulking of as muchof the tumor as possible and sampling of lymph nodesand other tissues in the pelvis and abdomen that aresuspected of harboring cancer. After the surgicalprocedure, treatment may be one of the following: 1)

combination chemotherapy with or without radiationtherapy or 2) combination chemotherapy.


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Stage III

Treatment is the same as for Stage II ovarian cancer.Following the surgical procedure, the patient may eitherreceive combination chemotherapy possibly followed byadditional surgery to find and remove any remainingcancer.


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Stage IV

CYTOREDUCTIVE SURGERY/DEBULKING:

surgery to remove as much of the tumor aspossible.

Most researchers consider residual disease of


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Trial of 146 patients with stage III and IV ovariancancer treated with cisplatin at Rosewell park

Cancer Institute:

SIZE OF RESIDUAL DISEASE SURVIVAL

5 YEARS 8 YEARS

2 CMS 13% 8.7%


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CHEMOTHERAPY

Prolongs remission and survival

Also used for palliative treatment in advanced nrecurrent disease

Administered in all cases beyond stage Ia

Earlier single agents were used, nowadays combinationtherapy is favoured


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CHEMOTHERAPY

No chemotherapeutic agent kills all cancer cells in onetreatment ,Tf treatment needs to be repeated severaltimes

All agents used should be active against that particulartumor

should have different modes of action to avoid drugresistance n should have differenr mechanisms oftoxicity.


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CHEMOTHERAPY

This allows each of them to be used as nearv to the fulldose as possible.

Drugs are given at 3 weeks intervals

Intraperitoneal chemotherapy is also done


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The initial treatment of ovarian cancer is called first-line therapy.

If the cancer continues to grow with first-line therapy orreturns after first-line therapy, additional treatment,called second-line therapy, may be administered.

If the tumor continues to grow after second-linetherapy, the next therapy is called third-line therapy,and so on.


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First-Line Chemotherapy

First-line chemotherapy for ovarian cancer typicallyconsists of two drugs given together. The combination=paclitaxel + platinum drugeither carboplatin orcisplatin.

Select women may benefit from administration ofchemotherapy directly into the abdomencalledintraperitoneal therapyin addition to conventionalintravenous administration.


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Second-Line Chemotherapy

The choice of drugs for second-line therapy dependslargely on which drugs were administered for first-linetherapy and how long it has been since the first-linetherapy was stopped.

chemotherapy drugs) for the treatment of ovariancancer that has returned:

GEMZAR (gemcitabine HCl for injection) plus anotherchemotherapy, carboplatin, is indicated ,6 months aftertheir first-line therapy;


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Second-Line Chemotherapy

Hycamtin (topotecan HCl for injection) is indicated as a

single agent (one drug) for the treatment of ovariancancer upon failure of first-line therapy;

and Doxil (doxorubicin HCl liposome injection) is

approved for use to treat women whose cancer hasreturned following first-line therapy.


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NICE guidelines for the use ofchemotherapy

It is recommended that paclitaxel in combination witha platinum-based compound or platinum-basedtherapy alone (cisplatin or carboplatin) are offered as

alternatives for first-line chemotherapy (usuallyfollowing surgery) in the treatment of ovarian cancer.

When relapse occurs after an initial (or subsequent)

course of first-line chemotherapy, additional coursesof treatment should be considered, using differenttreatment options.


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NICE guidelines for the use ofchemotherapy (contd..)

The following definitions are used by NICE: Platinum-sensitive ovarian cancer: disease that responds to first-line

platinum-based therapy but relapses 12 months or more aftercompletion of initial platinum-based chemotherapy.

Partially platinum-sensitive ovarian cancer: disease that responds tofirst-line platinum-based therapy but relapses between 6 and 12months after completion of initial platinum-based chemotherapy.

Platinum-resistant ovarian cancer: disease that relapses within 6

months of completion of initial platinum-basedchemotherapy.Platinum-refractory ovarian cancer: disease that doesnot respond to initial platinum-based chemotherapy.


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NICE guidelines for the use ofchemotherapy (contd)

Paclitaxel in combination with a platinum-based compound(carboplatin or cisplatin) is recommended as an option for thesecond-line (or subsequent) treatment of women with platinum-sensitive or partially platinum-sensitive advanced ovarian cancer,

except in women who are allergic to platinum-basedcompounds.

Single-agent paclitaxel is recommended as an option for thesecond-line (or subsequent) treatment of women with platinum-refractory or platinum-resistant advanced ovarian cancer, andfor women who are allergic to platinum-based compounds.

PLDH (pegylated liposomal doxorubicin hydrochloride) isrecommended as an option for the second-line (or subsequent)treatment of women with partially platinum-sensitive, platinum-resistant or platinum-refractory advanced ovarian cancer, andfor women who are allergic to platinum-based compounds.


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NICE guidelines for the use ofchemotherapy(contd.)

Topotecan is recommended as an option for second-line

(or subsequent) treatment only for those womenwith platinum-refractory or platinum-resistantadvanced ovarian cancer, or those who are allergicto platinum-based compounds, for whom PLDH and

single-agent paclitaxel are considered inappropriate.


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REGIMENS IN OVARIAN CANCER

REGIMEN DOSE

CP CISPLATIN

PACLITAXEL

75 mg/sq.m

135-175mg/sq.m

CT CARBOPLATIN

PACITAXEL

AUC=5

135-175mg/sq.m

DC CISPLATIN

CYCLOPHOSPHAMIDE

75mg/sq.m

750mg/sq.m

CAP CYCLOPHOSPHAMIDE

DOXORUBICIN

CISPLATIN

600mg/sq.m

50mg/sq.m

75mg/sq.m

BEP BLEOMYCIN

ETOPOSIDE

CISPLATIN

10mg/sq.m x 3 days

20mg/sq.m x 5days

100mg/sq.m


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REGIMEN FOR NON-EPITHELIAL TUMORS

VAC Vincistrene

VBC

BEP


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SIDE EFFECTS


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While chemotherapy drugs kill cancer cells, they alsodamage some normal cells, causing side effects. These side

effects will depend on the type of drugs given, the amounttaken, and how long treatment lasts. Temporary sideeffects might include the following:

nausea and vomiting loss of appetite hair loss hand and foot rashes

kidney or nerve damage mouth sores


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an increased chance of infection (from a shortage of

white blood cells)

bleeding or bruising after minor cuts (from a shortage ofplatelets)

tiredness (from low red blood cell counts)


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RADIOTHERAPY:

Now, has a very small role since platinum basedprotocols and paclitaxel have improved the median

survival.

-However it can be used as a palliative treatment formetastatic bone or brain lesions or of localizedrecurrence to alleviate the pain.


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Also used in recurrent germ cell tumors especiallydysgerminomas which is very radiosensitive.

Radioactive isotopes of gold-Au198 and phosphorus-P32have been used intraperitoneally along with externalradiotherapy.

However theres no improvement in survival rate.

High incidence of bowel complications have been noted.


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Recurrent Ovarian EpithelialCancer

Detection of Recurrent Disease

Second-Look Surgery


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Second-Look Surgery

The use of second-look surgery can help diagnose andmanage ovarian cancer.

evidence of enhanced survival after this procedure islacking.

It is defined as re-exploration n patients with advancedstage III and stage IV ovarian cancer after a standardcourse of chemotherapy have no clinical, biochemical, roradiologic evidence of disease


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The findings of second-look surgery are:

microscopically positive (grossly negative, butmicroscopically positive)

macroscopically positive (grossly and pathologicallypositive)


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Treatment of Recurrent Cancer

Patients who develop recurrent cancer despite surgeryand primary chemotherapy, and will be given salvagechemotherapy, may be placed into one of threegroups (A-C):


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GROUP A

are patients resistant to primary therapy and haveshown tumor growth during treatment. This persistingtumor is considered to be refractory i.e. have absoluteplatinum-resistance. Secondary non-cross resistantchemotherapies or biological therapies should be

considered.


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GROUP B

are patients who respond well to initial chemotherapy,but develop recurrent cancer within months after theend of primary care. This group with relatively platinumresistant tumor has an intermediate prognosis.


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GROUP C

are patients who showed a good response to primarychemotherapy, and did not develop recurrent cancer formore than 6 months after the end of primary treatment.This group with platinum-sensitive tumor shows the bestresponses to re-treatment with a platinum-containing

regimen.


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prognosis

Overall 5-year survival in ovarian epithelial carcinoma is low becauseof the preponderance of late-stage disease at diagnosis. Stage I and II: 80-100% Stage III: 15-20% Stage IV: 5%

Patients under 50 in all stages have considerably better 5-yearsurvival than older patients (40% compared to 15%)

Dysgerminomas treated by surgery and radiation have an excellentcure rate in both early and late-stage disease

Endodermal sinus tumour has poor prognosis.


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prevention

Diet: a high-fat diet may play a role in theaetiology of ovarian cancer.

Oral contraceptives appear to reduce the risk ofovarian cancer for up to 10 years followingcessation of use. This protective effect appearsto apply to patients with BRCA mutations aswell.

Patients who have used fertility drugs should becounselled as to their possible increase in risk ofovarian cancer.


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TREATMENT OF BENIGNTUMORS

Diagnostic tests include laboratory blood studies and pelvicexamination. Usually, ultrasound studies with and without bloodflow measurements to the involved ovary are used for diagnosis andto help determine the best therapy. Laparoscopy is required in somecases, and rarely, a CT scan or MRI may be recommended.

Treatment may not be necessary, except to have regular pelvicexaminations so the tumor's growth can be monitored.

Some tumors require surgery to diagnose accurately, ruling outmalignancy, or to treat. If one ovary must be removed, normalconception and childbirth is possible as long as a normal ovaryremains on the other side.


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TREATMENT OF BENIGNTUMORS

Germ cell tumors are treated with surgery and multi-agent chemotherapy in most cases

Advanced epithelial ovarian cancer is very sensitive tochemotherapy with responses in the range of 70-80% tofirst-line chemotherapy. The majority, however, relapseand ultimately die of chemotherapy-resistant disease.


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Treatment of Sensitive Cancer

Patients with recurrent chemotherapy-sensitive disease are usuallytreated again with primary chemotherapy usuallycarboplatin/paclitaxel, but toxicity must also be taken intoconsideration.

If carboplatin or cisplatin was used alone for primary therapy, taxolshould be considered for salvage chemotherapy.

For low-volume disease, intraperitoneal chemo- or radiotherapy can

be considered. These patients are also candidates for trials of highdose chemotherapy with autologous bone marrow support.


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Ovarian tumors its staging and management